Download The Career of Harry B. Gray

The Career of Harry B. Gray: Efficient Electron Transfer in Natural Redox Machines MacMillan Group Mee?ng February 13, 2013 Robert J Comito CV of Harry B. Gray  Education"
 1957 B.S. Western Kentucky State University "
 1960 PhD Northwestern University with Fred Basolo and R.G. Pearson"
 1960-1961 NSF Postdoctoral Fellow at the University of Copenhagen
with C.J. Ballhausen"
 Notable awards"
 1986 National Medal of Science "
 1991 Priestly Medal (American Chemical Society)"
 2000 Harvey Prize (Technion-Israel Institute of Technology)"
 2004 Wolf Prize for Chemistry"
 2009 Welch Award for Chemistry"
 Famous Students: Dan Nocera (MIT), Herbert Holden Thorp
(UNC Chapel Hill), Mark Stephen Wrighton (WSU St Louis) CV of Harry B. Gray  Honorary appointments"
 American Academy of Arts and Sciences (member
1979, fellow 1989)"
 Royal Academy Göteborg (foreign member 1995)"
 Royal Society of Great Britain (foreign member 2000)"
 Royal Society of Chemistry (honorary fellow 2005)"
 ACS fellow (2009)"
 Academic positions"
 Columbia University (1960-1966)"
 California Institute of Technology (1966-present)"
 Arnold O. Beckman Professor of Chemistry (1981present, Caltech)"
 Founding director of Beckman Institute and Principal
Investigator at the B.I. Laser Resource Center"
 Solar fuels director at CCI Solar (aka, General of the
Solar Army)"
A Prolific Postdoc Inorg. Chem. 1962, 1, 111-122.!
"The Ballhausen-Gray model for metal-oxo bonding remains the
standard to this day...enabl[ing] a generation of computational
chemists to perform molecular orbital calculations of the
structures and reactivities of inorganic molecules."
Jay R Winkler (former Gray student and collaborator at BILRC)"
“A Celebration of Harry B Grayʼs 75th Birthday” Coorc. Chem.
Rev. 2011, 255, 617-618."
Electronic Structure of the Vanadyl Ion  A ligand field model of vanadyl ion (VO+) is
inconsistent with magnetic and spectroscopic
measurements"
 A symmetry based MO treatment of VO+ accurately
predicts the observed electronic energy levels"
A ligand field description of VO(OH2)5+"
Ballhausen-Gray MO
description of VO(OH2)5+"
Ballhausen, C.J.; Gray, H.B. Inorg. Chem. 1962, 1, 111-122.!
Longstanding Research Interests Bonding in metal complexes:"
Bioinorganic reaction
mechanisms:"
Bercaw, J.E.; Durrell, A.C.; Gray, H.B.; Green, J.C.; Hazari, N.
Inorg. Chem. 2010, 49, 1801-1810."
Dynamics of protein folding
and unfolding:"
Dunn, A.R.; Dmochowski, I.J. Bilwes, A.M.; Gray, H.B.; Crane,
B.R.; Proc. Natl. Acad. Sci. 2001, 98, 12420-12425."
Contakes, S.M. Le Nguyen, Y.H.; Gray, H.
B.; Glazer, E.C.; Hays, A. M.; Goodin, D.
B. Struct. Bond. 2007, 123, 177-203
Dye-­‐Sensi?zed Solar Cells (DSSCs) Outline of DSSC operation:"
Using LLCT exitation improves charge separation
and reduces nonproductive charge recombination:"
Photochem. & Photobiol. 2006, 5, 871-873."
Efficient electron injection depends on picosecond
electron transfer from dye to TiO2 valence band"
TiO2: a cheap, abundant band
gap material"
Robertson, N. Angew. Chem. Int.
Ed. 2006, 45, 2338-2345."
J. Phys. Chem. B. 2002, 106, 9347-9358."
Catalysts for Efficient Water SpliWng Solar materials for
hydrogen production:"
Molecular catalysts for
photolytic hydrogen:"
Mechanism of water
splitting:"
H+ reducing
catalyst"
photoredox
catalyst"
Gray, H.B. Nat. Chem. 2009, 1, 7."
Dalton Trans. 2012, 41, 13060-13073."
J. Am. Chem. Soc. 2010, 132,
1060-1065"
A major theme: design features for efficient electron transfer"
This Talk: Electron Transfer in Natural Systems Energy diagram for photosynthesis"
Bacterial photosynthetic redox center: an
efficient natural redox machine"
 In order for complex biochemical processes to be efficient, electron transfer (ET) must:"
 Be fast and cover great distances"
 Have high directional control"
 Have small – ΔG associated with individual steps"
What controls the efficiency of ET in natural redox machines?"
Electron Transfer Theory kET =
4!3
h2"kBT
1/2
HAB2 e
- (#G° + ")2 / 4"kBT
For a semiclassical description of tunneling "
 Reorganization energy (λ)"
 The energy of the reactants at equilibrium nuclear configuration of products"
 Changes in solvation, coordination, and conformation upon electron transfer all will increase λ"
 Electron transfer fastest when – ΔG = λ"
 Weak dependence of kET on absolute temperature (T)"
 Small drops in rate at cryogenic T usually indicates tunneling mechanism"
 Electronic coupling (HAB, QM definition)"
 Measure of orbital overlap, distance, and ability of intervening medium to transmit electrons"
Gray, H. B.; Winkler, J. R. Annu. Rev. Biochem. 1996, 65, 337-361.
Laser Flash Quench Studies Design plan:"
bioconjugation of
photocatalyst"
2+
N
N
N
Ru
N
N
N
Cofactor +
Laser Flash Quench Studies Design plan:"
bioconjugation of
photocatalyst"
laser pulse
photoexcitation "
2+
2+*
N
N
N
Ru
N
N
N
N
N
N
Ru
N
N
N
eCofactor +
Cofactor +
intermediates
followed by timeresolved
spectroscopy"
Laser Flash Quench Studies Design plan:"
bioconjugation of
photocatalyst"
laser pulse
photoexcitation "
intermediates
followed by timeresolved
spectroscopy"
2+
N
N
N
Ru
N
N
N
kinetic modelling"
Cofactor
+
Rates of electron
transfer steps obtained"
Laser Flash Quench Studies Design plan:"
bioconjugation of
photocatalyst"
laser pulse
photoexcitation "
intermediates
followed by timeresolved
spectroscopy"
2+
N
N
N
Ru
N
N
N
kinetic modelling"
Cofactor
+
Rates of electron
transfer steps obtained"
Structural variation
provides trends in
ET rates"
Laser Flash Quench Studies Design plan:"
Bioconjuga?on of Photocatalysts 2+
2+
N
N
N
N
Ru
N
N
N
NH
OH2
N
N
N
N
NH
NH
NH
coordinatively
unsaturated
precatalyst"
N
Ru
site-specific
histidine mutant"
covalently bound
photocatalyst"
 Choice of photocatalyst to optimize ΔG and λ"
 Follow catalyst oxidation state and excitation state by time resolved spectroscopy"
 UV/Vis, luminescence for bpy, terpy, phenanthroline complexes"
 IR for carbonyl complexes, e.g. Re(phen)(CO)3(His)+"
Temperature Dependance of kET  In photosynthetic reaction center (PRC), primary ET rate is same over large temperature range"
 Cooling from 300K to 4K, primary ET rate increases by a factor of 3"
R. viridus primary charge separation in PRC"
R. sphaeroides reduced quinone to oxidized special
pair transfer in PRC"
A more representative temperature trend
among common ET enzymes"
Skov, L. K.; Pascher, T.; Winkler, J. R.; Gray, H. B. J. Am. Chem. Soc. 1998, 120, 1102-1103.
Temperature Dependance of kET  In photosynthetic reaction center (PRC), primary ET rate is same over large temperature range"
 Cooling from 300K to 4K, primary ET rate increases by a factor of 3"
 Model system: Ru-modified P. aruginosa azurins, "
 Azurins are blue copper proteins involved in bacterial arsenic metabolism "
 Ru(bpy)2(im)(His83)azurin fixes photocatalyst and Cu reaction center across a beta sheet"
Reaction center of
Ru(His83)azurin"
Skov, L. K.; Pascher, T.; Winkler, J. R.; Gray, H. B. J. Am. Chem. Soc. 1998, 120, 1102-1103.
Temperature Dependance of kET  Laser flash quench studies follow modeled temperature trend down to 240K"
 Significant increase in rate at cryogenic temperatures not explained by any model assuming
constant λ, ΔG, and HAB"
 Temperature dependence of one of these parameters"
kET =
4!3
h2"kBT
1/2
HAB2
e
- (#G° + ")2 / 4"kBT
What accounts for the anomalous cryogenic increase in reaction rate?"
Skov, L. K.; Pascher, T.; Winkler, J. R.; Gray, H. B. J. Am. Chem. Soc. 1998, 120, 1102-1103.
Electron Tunneling in Single Crystals  For family of photocatalyst-bound azurins, rate in crystal is similar to that in solution"
 Structural comparison in Cu(I) and Cu(II) proteins reveals minor change in bond distances"
 Redox active center well shielded from solvent"
Coordination bond
distances change <
0.08Å between Cu(I)
and Cu(II)"
Low solvent accessibility at
active site"
Crane, B.R.; DiBilio, A.J.; Winkler, J. R.; Gray, H. B. J. Am. Chem. Soc. 2001, 123, 11623-11631.
Electron Tunneling in Single Crystals Conclusions:"
 Fixed coordination and solvent exclusion minimize λ"
 Confirmed by large self-exchange reaction"
 Essential for fast ET with low —ΔG°"
 More compact structure at low T further minimizes λ,
accounting for cryogenic increase in kET. "
But minimizing λ comes at a price:"
 Burying redox cofactors in proteins means that
electron transfer must occur at great distances between
Hydrogen bonding network
distributes small structural
changes about protein"
redox partners"
Crane, B.R.; DiBilio, A.J.; Winkler, J. R.; Gray, H. B. J. Am. Chem. Soc. 2001, 123, 11623-11631.
Distant Electronic Coupling tunneling barrier"
kET =
4!3
h2"kBT
1/2
HAB2
e
distance (r)"
- (#G° + ")2 / 4"kBT
Rate strongly dependent on HAB"
E
 For square barrier tunneling model (constant
barrier height) HAB decays exponentially with
distance:"
HAB(r) = HAB(r0) e
exponential "
decay"
- ! (r-r0) / 2
2+
 Decay contant (β) depends on barrier height"
Fe
 β = 3-5 Å-1 in a vacuum"
 β = 1.7 Å-1 in a H2O"
Smalley
et al. : "
 β = 1.0 Å-1 across a saturated alkane"
en
S
Au SAM"
Hopfield, J.J. Proc. Natl. Acad. Sci. 1974, 71, 3640-3644.
Smalley, J. F. et al. J. Am. Chem. Soc. 2003, 125, 2004.
Measuring Distance Dependence Design Plan:"
 Prepare a family of photocatalyst-bound proteins with
systematically donor-acceptor distances (constant λ,
ΔG°, and HAB(r0))"
 Measure kET and determine decay constants (β)"
Various histidine substituted mutants of
P. aeruginosa azurins for coordination
with Ru(bpy)2(im)2+ "
How does intervening protein structure affect electronic coupling (HAB)?"
Gray, H.B.; Winkler, J.R. Annu. Rev. Biochem. 1996, 65, 537-561.
Measuring Distance Dependence intercept ="
rate at VDW"
contact"
Slope"
= β"
Result:"
 Obtained β = 1.1 Å-1 for a azurin ET"
 Hopfield et al. predicts β = 1.4 Å-1 for square tunneling
barrier view of protein (ie, does not account for secondary
structure)"
 Azurin structure dominated by β-sheet"
Gray, H.B.; Winkler, J.R. Annu. Rev. Biochem. 1996, 65, 537-561.
Distance Dependence on an α-­‐Helix Azurin (β = 1.1 Å-1)"
Mb and RC (β = 1.4 Å-1)"
 Same analysis on two myoglobins (Mb) and the
reaction center (RC) from the photosynthetic reaction
Various histidine substituted mutants for
coordination with Ru(bpy)2(im)2+ on
myoglobin, an α–helical protein"
center (PRC)"
 Measures electronic coupling across α–helix "
 Obtained β = 1.4 Å-1, "
Gray, H.B.; Winkler, J.R. Annu. Rev. Biochem. 1996, 65, 537-561.
Distance Dependence on an α-­‐Helix Azurin (β = 1.1 Å-1)"
Mb and RC (β = 1.4 Å-1)"
 The range around each slope define a secondary
structure “zone”"
electron transfer rates through a variety of
proteins"
 Plotting electron transfer on several proteins in this
way, zones predict secondary structure well"
Gray, H.B.; Winkler, J.R. Annu. Rev. Biochem. 1996, 65, 537-561.
Distance Dependence on an α-­‐Helix Various site-specific
histidine mutants of
cytochrome c, a
protein with both α–
helices and β-sheets"
 The range around each slope define a secondary
structure “zone”"
electron transfer rates through a variety of
proteins"
 Plotting electron transfer on several proteins in this
way, zones predict secondary structure well"
How does secondary structure affect electronic coupling?"
Gray, H.B.; Winkler, J.R. Annu. Rev. Biochem. 1996, 65, 537-561.
Theore?cal Analysis of Electronic Coupling 2+
 Decay constants (β) determined by:"
Fe
 Barrier height (E of path)"
 Directness of path (effective distance)"
en
alkane bridge: a direct
path connected by
strong covalent bonds"
S
 Number of paths in 3-dimensions"
 Computational approach:"
 Divide tunneling path into conduction
zones connected by bonds, H-bonds,
and through space jumps"
 Parameterize coupling decay for each
link"
 Search algorithm identifies most likely
path and coupling decays for each link"
Regan, J.J.; DiBilio, A.J.; Langen, R.; Skov, L.K.; Winkler, J.R.; Gray, H.B.; Onuchic, J.N.; Chem & Biol. 1995, 2, 489-496.
Theore?cal Analysis of Electronic Coupling Results:"
 Conduction best through strong, covalent
bonds"
 With hydrogen bonds, stronger
bond means better conducion"
 Through space jumps have the
highest coupling decays"
 Effective tunneling distance (σl) depends
on shape of the path"
 Longer for less direct routes"
Tunneling pathways along the
azurin backbone"
Regan, J.J.; DiBilio, A.J.; Langen, R.; Skov, L.K.; Winkler, J.R.; Gray, H.B.; Onuchic, J.N.; Chem & Biol. 1995, 2, 489-496.
Basis for Difference in Decay Constants Comparison:"
 α-helices:"
 Weaker hydrogen bonds (νCO = 1680-1700
cm-1)"
 Less direct pathway along backbone means
greater effective tunneling distance (σl) "
 Larger β, more “insulating”"
  β-sheets:"
 Stronger hydrogen bonds (vCO = 1630 cm-1)"
 More direct pathway along backbone"
 Smaller β, more “conducting”"
Calculated path length along
α–helix and β–sheet"
Conducting channels built into secondary structure provide directional control."
Regan, J.J.; DiBilio, A.J.; Langen, R.; Skov, L.K.; Winkler, J.R.; Gray, H.B.; Onuchic, J.N.; Chem & Biol. 1995, 2, 489-496.
Hopping: a Mechanis?c Alterna?ve Reaction scheme:"
D I A
D I A
hv
hv
*D I A
D I A
D I A
electron hopping
*D I A
D I A
D I A
hole hopping
 Kinetics shows hopping is much more sensitive to temperature than single-step tunneling"
 However, single-step tunneling over 20Å is prohibitively slow in proteins, yet ET sometimes
required over greater distances "
Objective:"
 Observe hole hopping through an aromatic side
chain in a suitably substituted azurin"
 Identify structural featured that control hopping in
proteins"
ReI(CO)3(dmp)(His124)(Trp122)AzurinCuII"
Warren, J.J.; Ener, M.E.; Vlcek, A.; Winkler, J.R.; Gray, H.B. Coord. Chem. Rev. 2012, 256, 2478-2487.
Hopping Through a Func?onalized Azurin Hopping in ReI(CO)3(dmp)(His124)(Trp122)AzurinCuII:"
 Hopping route much faster than that predicted for single step ET (19Å ReI to CuII)"
 No hopping observed for Phe124, Tyr124, and Lys124 analogs"
 Does not work for deprotonated indole (too exothermic for second ET)"
Warren, J.J.; Ener, M.E.; Vlcek, A.; Winkler, J.R.; Gray, H.B. Coord. Chem. Rev. 2012, 256, 2478-2487.
Hopping Through a Func?onalized Azurin I
I
G
D
!G
I
I
D I A
D I A
A
D I A
Alternative energy scenarios for hole hopping"
 Oxidation-coupled deprotonation of indole would also make indole oxidation too exothermic"
 No residues capable of directly deprotonating the indole, so it works at physiological pH"
Hopping efficiency is very sensitive to the ΔG° of initial ET"
Warren, J.J.; Ener, M.E.; Vlcek, A.; Winkler, J.R.; Gray, H.B. Coord. Chem. Rev. 2012, 256, 2478-2487.
Hopping Maps For Subs?tuted Azurins  Relationship between hopping
rate and ΔG° for two steps can
be modeled and represented with
hopping maps"
 Can determine for what
ΔG° would hopping be
faster than direct tunneling"
Warren, J.J.; Ener, M.E.; Vlcek, A.; Winkler, J.R.; Gray, H.B. Coord. Chem. Rev. 2012, 256, 2478-2487.
Hopping in DNA Photolyase A hopping pathway for DNA photolyase?"
 DNA photolyase is involved in bacterial repair of UVdamaged DNA"
 Site directed mutants show that all three tryptophans are
required for substrate reduction"
FADH-­‐, a highly reducing natural photoredox catalyst  Also, no nearby base to deprotonate oxidized
intermediates"
 Initial computations suggest hopping mechanism too slow"
Warren, J.J.; Ener, M.E.; Vlcek, A.; Winkler, J.R.; Gray, H.B. Coord. Chem. Rev. 2012, 256, 2478-2487.
Hopping in DNA Photolyase Hopping map with λ = 0.8 eV"
Hopping map with λ = 0.5 eV"
Proper reorganiza?on energy needed for hopping to work Hopping requires structural in addition to energetic fine tuning"
Warren, J.J.; Ener, M.E.; Vlcek, A.; Winkler, J.R.; Gray, H.B. Coord. Chem. Rev. 2012, 256, 2478-2487.
Hopping in Other Natural Systems Proposed ET pathway in E. coli
ribonucleotide reductase"
Tryptophans positioned for hopping in MauG"
Warren, J.J.; Ener, M.E.; Vlcek, A.; Winkler, J.R.; Gray, H.B. Coord. Chem. Rev. 2012, 256, 2478-2487.
Hopping in the Photosynthe?c Reac?on Center Map for hopping through bacteriochlorphyll"
 Hopping an essential feature of ET
transport in photosynthesis"
 Hopping maps suggest that ΔG°ʼs
Bacterial photosynthe?c reac?on center. Special pair (P), bacteriochlorphyll (B), bactereophenphy?n (H), and quione (Q) are highly optimized for hopping
efficiency"
Warren, J.J.; Winkler, J.R.; Gray, H.B. Coord. Chem. Rev. 2013, 257, 165-170.
Hopping in the Photosynthe?c Reac?on Center  Two branches, L and M, from the special pair"
 Same cofactors"
 Small difference in positioning and
nearby amino acids"
 L branch is productive, but M completely
inactive"
What controls electron flow at this
critical bifurcation in photosynthetic
electron transfer?"
Bacterial photosynthe?c reac?on center. Special pair (P), bacteriochlorphyll (B), bactereophenphy?n (H), and quione (Q) Warren, J.J.; Winkler, J.R.; Gray, H.B. Coord. Chem. Rev. 2013, 257, 165-170.
Hopping in the Photosynthe?c Reac?on Center  Different amino acid environment results in slight changes in cofactor reduction potentials"
 Hopping maps suggest that ΔG°ʼs are poorly paired for hopping in the M branch"
 Direct electron transfer from the special pair (PM) to bacteriophenphytin (HM) too slow to
make up for loss of hopping electron transfer"
Map for hopping through
bacteriochlorphyll in the M branch"
Measured energy levels in the M and L branch Hopping with carefully optimized ΔG°ʼs controls electron flow in the PRC"
Warren, J.J.; Winkler, J.R.; Gray, H.B. Coord. Chem. Rev. 2013, 257, 165-170.
Molecular Wires Getting into the active site"
 Electron transfer often occurs between enzyme-bound substrate and buried metal cofactor"
 Electronic manipulation can be difficult from “outside” the protein because of long tunneling
distances"
enzyme
S
enzyme
M+
ET
S+
M
Electron transfer in a buried ac?ve site Hartings, M.R.; Kurnikov, I.V.; Dunn, A.R.; Winkler, J.R.; Gray, H.B.; Ratner, M.A. Coord. Chem. Rev. 2010, 254, 248.
Molecular Wires Design Plan:"
 Connect ligands with an affinity for active site to redox manipulable functional group outside
the protein via an efficient tunneling wire"
2+
N
N
N
Ru
N
N
N
enzyme
M+
Ru(bpy)32+ connected to heme ac?ve site via molecular wire Hartings, M.R.; Kurnikov, I.V.; Dunn, A.R.; Winkler, J.R.; Gray, H.B.; Ratner, M.A. Coord. Chem. Rev. 2010, 254, 248.
Molecular Wires for Voltammetry Measuring redox potentials"
 A. globiformis amine oxidase (AGAO)
AGAO
O
HO
oxidizes amines to aldehydes via an
active site 2,4,6-trihydroxyphenylalanine
AGAO
O
OH
O
O
NEt2
NEt2
quinone (TPQ)"
+ 2e-
 Measuring TPQ redox potentials not
+ 2H+
possible with standard electrode"
 Molecular wire bridges 20Å hydrophobic
channel to allow tunneling from electrode
to TPQ"
 β = 0.4-0.6 Å-1 through phenylenealkyne bridges"
S
Au electrode
S
Au electrode
Molecular wires conduct electrons for cathodic reduc?on Hess, C.R.; Juda, G.A.; Dooley, D.M.; Amii, R.N.; Hill, M.G.; Winkler, J.R.; Gray, H.B. J. Am. Chem. Soc. 2003, 125, 7156-7157.
Molecular Wires for Voltammetry Measuring redox potentials"
 A. globiformis amine oxidase (AGAO)
oxidizes amines to aldehydes via an
active site 2,4,6-trihydroxyphenylalanine
quinone (TPQ)"
 Measuring TPQ redox potentials not
AGAO-­‐molecular wire complex possible with standard electrode"
 Molecular wire bridges 20Å hydrophobic
channel to allow tunneling from electrode
to TPQ"
 β = 0.4-0.6 Å-1 through phenylenealkyne bridges"
Successful CV run with molecular wire Hess, C.R.; Juda, G.A.; Dooley, D.M.; Amii, R.N.; Hill, M.G.; Winkler, J.R.; Gray, H.B. J. Am. Chem. Soc. 2003, 125, 7156-7157.
Reduc?on of a Heme Cofactor Heme oxidations in p450cam"
 Efficient for hydroxylation of hydrophobic
substrates, especially camphor (hence “cam”)"
 Mechanism of heme oxidations well-studied
and key intermediates like oxoferryl (7)
characterized"
 Transient intermediates, such as reduced
PcysFeII(OH2) (3) cannot be isolated or observed
under reaction conditions"
Currently accepted mechanism for p450 hydroxyla?ons Contakes, S.M. Le Nguyen, Y.H.; Gray, H. B.; Glazer, E.C.; Hays, A. M.; Goodin, D. B. Struct. Bond. 2007, 123, 177-203
Flash-­‐Quench Reduc?on of a Heme Cofactor 1+
2+*
N
N
N
Ru
N
N
N
N
N
N
Ru
N
N
N
n
OH2
N
n
OH2
Et
Et
N
Fe3+
N N
N
Q+
Q
Cys S
hv
ET
N
Fe3+
N N
Cys S
2+
2+
N
N
N
Ru
N
N
N
N
N
N
Ru
N
N
N
n
OH2
N
Hydrophobic ligand anchors head group to the ac?ve site Et
N
Fe3+
N N
Cys S
n
OH2
Et
N
Q
Q+
N
Fe2+
N N
Cys S
PcysFeII(OH2)
Flash quench mechanism for observa?on of PcysFeII(OH2) Photoreduction through a tunneling wire allows observation of PcysFeII(OH2)"
Hartings, M.R.; Kurnikov, I.V.; Dunn, A.R.; Winkler, J.R.; Gray, H.B.; Ratner, M.A. Coord. Chem. Rev. 2010, 254, 248.
Summary  Efficient electron transfer in biological systems involves"
 Fixed coordination and solvent exclusion to minimize reorganization energies (λ)"
 Conduction channels built into secondary structure"
 Hopping through intermediates optimally positioned spatially and energetically"
 A model was developed for predicting the energetic requirements for hopping in a redox machine"
 These principles were used to design molecular wires for redox manipulation of buried active site
cofactors"
In addressing high impact problems in energy conversion and fuel technology, the
principles of efficient electron transfer will be essential to chemical solutions to
tomorrowʼs technology needs."